To report the clinical and laboratory characterization of a case of multiple myeloma with low hypodiploid complex karyotyptic abnormalities.Cytogenetic examination of bone marrow performed by 24 h culture method. R-banding technique was used to analyze the karyotype. Interphase fluorescence in situ hybridization (FISH) was performed using chromosome probes such as 13q14, p53, Rb1, 1q21 and IgH/CCND1. The DNA content was detected by flow cytometry.Chromosome analysis revealed complex chromosomal rearrangement. Five cells had a low hypodiploid karyotype with 35 chromosomes. Three cells had the duplication of the low hypodiploid karyotype. Four cells had a normal karyotype. Monosomy 1, 13, 14, 17 and a mark chromosome 1 derived from chromosome 11 resulting in the amplication of CCND1 gene were confirmed by interphase FISH. Flow cytometric analysis displayed a low hypodiploid peak with the DNA index of 0.8426.These results indicated that the low hypodiploidy is a rare abnormality in multiple myeloma. Interphase FISH is a reliable method for detecting molecular abnormalities in multiple myeloma.
To compare the signal patterns of dual color extra-signal BCR/ABL probe (ES-FISH) and dual color dual fusion BCR/ABL probe (D-FISH) in the fluorescence in situ hybridization (FISH) detection of Ph-positive leukemia, and to explore their diagnostic value.ES-FISH probe and D-FISH probe were used, respectively, to detect the BCR/ABL fusion gene in 74 cases with typical t(9;22)(q34;q11) and 37 cases with variant t(9;22)(q34;q11) translocation or complex karyotypic abnormalities containing Ph translocation.The BCR/ABL fusion gene in all cases with typical t(9;22)(q34;q11) could be detected by both FISH probes. D-FISH had a signal pattern of 1O1G2F, while ES-FISH showed a signal pattern of 2O1G1F. ES-FISH enables the minor breakpoint cluster region to be identified in 9 cases (12.2% ) of Ph-positive leukemia, whereas D-FISH could not differentiate the minor breakpoint cluster region from major breakpoint cluster region. D-FISH could distinguish simple ABL gene deletion from simultaneous deletion of the ABL and BCR genes in 8 cases (10.8%) of Ph-positive leukemia patients, but ES-FISH could not. For variant Ph translocation or complex karyotypic abnormalities containing Ph translocation, each FISH probe showed four or six types of signal pattern, most of which were atypical. The exact interpretation was dependent on conventional karyotypic analysis and FISH on metaphases.ES-FISH and D-FISH probes displayed different signal patterns in Ph-positive leukemia due to their differences in size and covered regions. ES-FISH and D-FISH probes may be selected as better probe for Ph-positive acute lymphocytic leukemia and Ph-positive chronic myeloid leukemia, respectively. When imatinib was used for treatment, there was no preference between ES-FISH and D-FISH probe, because major breakpoint cluster region, minor breakpoint cluster region and partial sequence deletion of derivative chromosome 9, would not affect the prognosis of Ph-positive leukemia. However, considering that ES-FISH probe has a better cost-performance than D-FISH probe does, it is recommended as first choice.
Abstract Background: To the best of our knowledge, few reports are available at home and abroad on autoimmune haemolysis occurring after operation of gastric cancer complicated with drug-refractory idiopathic thrombocytopenic purpura (ITP)(Table 1). The treatment process in this case is usually risky, and multidisciplinary collaboration is often required. Therefore, the case report aims to improve the awareness of the perioperative management of this type of patients. Case presentation: A 69-year-old male admitted to the hospital for "anaemia" was diagnosed with gastric adenocarcinoma after gastroscopy and biopsy. This diagnosis was confirmed to be an early stage by abdominal CT imaging. However, the patient had an extremely low platelet level and a history of hormone therapy. Moreover, administration of thrombopoietin and immunoglobulin was ineffective for treatment. After transfusion of aphaeretic platelets, laparoscopic total gastrectomy with D2 lymphadenectomy and splenectomy were performed. Anastomotic bleeding and autoimmune haemolysis occurred after the operation. Haemolytic symptoms were spontaneously relieved after a period of hospitalisation. Conclusion: This case involved many disciplines, and revealed the interaction and mutual promotion of gastric cancer, ITP and autoimmune haemolysis, but further relationships need to be further investigated.
Fecal occult bloodtest (FOBT) plays an important role in the diagnosis of gastrointestinal diseases. The sensitivities of current FOBT methods are still not satisfactory. The aim of this study is to develop a combined human transferrin (HTf)-hemoglobin (HHb) lateral flow assay (LFA) for accurate and rapid FOBT.Monoclonal antibodies (MAbs) targeting HTf were developed by conventional methods and paired using LFA strips. The best HTf MAb pair was chosen according to the overall performance on testing limit and specificity. Meanwhile, HHb LFA strips were prepared using previously developed HHb MAbs. The testing limit and specificity were characterized. Based on the selected HTf MAb pair and the verified HHb MAb pair, combined HTf-HHb strips were developed. The combined HTf-HHb strips were used for FOBT of 400 human fecal samples, including 200 gastrointestinal bleeding specimens and 200 healthy subjects. For comparison, the homemade individual HTf and HHb strips, as well as three kinds of commercial FOBT strips, were also used for the FOBT.Two MAb pairs targeting HTf were developed for LFA. Two types of HTf strips were prepared accordingly. The type I was chosen due to its lower detection limit. Using the type I HTf MAb pair and the verified HHb- MAb pair, the combined HTf-HHb strips could detect the HTf at concentrations between 1 ng/mL and 1 x 106 ng/mL and the HHb between 10 ng/mL and 2.5 x 106 ng/mL. Compared to individual HTf and HHb strips and three kinds of commercial strips, the combined strips showed the highest diagnostic sensitivity in FOBT (96.0%). The specificity was a satisfactory 99%.Our combined HTf-HHb test strips are a very promising product for accurate and rapid FOBT.
We have observed that aggregation of human platelets, caused by activation of integrin alphaIIb beta3 and its consequent binding of fibrinogen, stimulates a novel pathway for synthesis of phosphatidylinositol 3,4bisphosphate, thereby activating protein kinase B/Akt. Such synthesis depends upon both the generation of phosphatidylinositol 3-phosphate (PtdIns3P), which is sensitive to wortmannin (IC50 7 nM) and calpain inhibitors, and the phosphorylation of PtdIns3P by PtdIns3P 4-kinase. We now report that a recently characterized C2 domain-containing phosphoinositide 3-kinase isoform (HsC2-PI3K) is present in platelets and a leukemic cell line (CHRF-288) derived from megakaryoblasts, and is likely to be responsible for the stimulated synthesis of PtdIns3P observed in platelets. HsC2-PI3K, identifiable by Western blotting and immunoprecipitatable activity, is sensitive to wortmannin (IC50 6-10 nM), requires Mg2+, and shows strong preference for PtdIns over PtdIns4P or phosphatidylinositol 4,5-bisphosphate as substrate. HsC2-PI3K is activated severalfold when platelets aggregate in an alphaIIb beta3-dependent manner or when platelet or CHRF-288 lysates are incubated with Ca2+. Activation is prevented by calpain inhibitors. CHRF-288, which cannot undergo activation of alphaIIb beta3 and thereby aggregate in response to platelet agonists, do not generate PtdIns3P or activate HsC2-PI3K under conditions that stimulate other phosphoinositide 3-kinases. HsC2-PI3K may thus be an important effector for integrin-dependent signaling.
Abstract Background: Risk stratification for normal karyotype acute myeloid leukemia remains unsatisfactory, which is reflected by the high incidence of leukemia relapse. This study aimed to evaluate the role of gene mutations and clinical characterization in predicting the relapse of patients with normal karyotype acute myeloid leukemia. Methods: A prognostic system for normal karyotype acute myeloid leukemia was constructed based on gene mutations, measurable residual disease, and clinical characteristics. A panel of gene mutations was explored using next-generation sequencing. The least absolute shrinkage and selection operator, and nomogram algorithm were used to build a genomic mutation signature (GMS) nomogram (GMSN) model that combines GMS, measurable residual disease, and clinical factors to predict relapse in 347 patients with normal karyotype acute myeloid leukemia from four centers. Results: Patients in the GMS-high group had a higher 5-year incidence of relapse than those in the GMS-low group ( P < 0.001). The 5-year incidence of relapse was also higher in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups ( P < 0.001). The 5-year disease-free survival and overall survival rates were lower in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups ( P < 0.001) as confirmed by training and validation cohorts. Conclusions: This study illustrates the potential of GMSN as a predictor of normal karyotype acute myeloid leukemia relapse.
Chronic myeloid leukemia (CML) is rare among children and adolescents. The early molecular response (EMR) is an important prognostic significance for adult CML patients. This study explored the impact of EMR on the prognosis in 40 children and adolescents with CML-CP treated with imatinib (IM). Our results showed that a high proportion of patients failed to achieve the BCR-ABL1/ABL1 International Scale (IS) ≤ 10% at 3 months. Children with a BCR-ABL1/ABL1 ≤ 10% at 3 months and <1% at 6 months increased the rate of achieving complete cytogenetic response (CCyR) and/or major molecular response (MMR) at 12 months compared to those with BCR-ABL1/ABL1 > 10%. With a median follow-up of 42 months, patients with BCR-ABL1/ABL1 ≤ 10% showed a better 4-year event-free survival (EFS). In summary, achieving BCR-ABL1/ABL1 IS ≤10% at 3 months and <1% at 6 months would increase the possibility of achieving MMR, CCyR at 12 months and had a better 4-year EFS. EMR is a reliable prognosticator for young CML patients treated with IM.
Risk stratification for normal karyotype acute myeloid leukemia (NK-AML) remains unsatisfactory, which is reflected by the high incidence of leukemia relapse. This study aimed to evaluate the role of gene mutations and clinical characterization in predicting the relapse of patients with NK-AML. A prognostic system for NK-AML was constructed. A panel of gene mutations was explored using next-generation sequencing. A nomogram algorithm was used to build a genomic mutation signature (GMS) nomogram (GMSN) model that combines GMS, measurable residual disease, and clinical factors to predict relapse in 347 patients with NK-AML from four centers. Patients in the GMS-high group had a higher 5-year incidence of relapse than those in the GMS-low group (p < 0.001). The 5-year incidence of relapse was also higher in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups (p < 0.001). The 5-year disease-free survival and overall survival rates were lower in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups (p < 0.001) as confirmed by training and validation cohorts. This study illustrates the potential of GMSN as a predictor of NK-AML relapse.
Abstract Imatinib (IMNB) is a promising type of chemotherapeutic agent that specifically targets tyrosine kinase pathway-dependent tumors. However, cardiotoxicity has been reported with clinical use of IMNB. The characteristics of IMNB-induced cardiac alterations are not completely defined. The present study sought to examine the influence of a concomitant disease such as hypertension on the cardiotoxic effects of IMNB. Groups of adult male SD or SHR were dosed with 50 (5/group) or 100 mg/kg (10/group) IMNB or water (10/group)(p.o.) daily for 14 days (dose of 50 mg/kg is approximately 2x recommended human dose of 600 mg/m2). Tissues and blood samples were collected 24 hours after the last dosing. The 100 mg/kg dose caused a slight reduction in the rate of body weight gain. Serum levels of glucose were decreased and alanine transaminase (ALT) were increased in both SD and SHR dosed with IMNB. Changes from control were most pronounced in SD given 100mg/kg IMNB (ALT=175% vs 118% and glucose=81% vs 91% compared to SHR). White blood cell counts were depressed in SHR but not in SD rats. Dose-dependent cardiac lesions were noted in the groups of SD and SHR given either dose of IMNB (blinded evaluation). Cardiac lesions were characterized by cytoplasmic vacuolization, myofibrillar loss, interstitial infiltration with chronic inflammatory cells and fibrosis (proliferation of myofibroblasts). Mean lesion scores (based on a scale of 0 to 3) were higher in SHR than in SD (100mg/kg-1.9 vs 1.25 and 50 mg/kg-1.5 vs 1.1, p<0.05)(Tukey-Kramer test). Increased serum levels of cardiac troponin I were detected in all IMNB-treated groups. The overall mean cTnI levels were higher in SHR (31.5, 41.3 and 53.9 pg/ml) compared to SD (6.8, 25 and 30 pg/ml) at the vehicle control, 50 and 100 mg/kg doses, respectively. These results indicate that hypertension as expressed in SHR appears to be a factor that can intensify the cardiotoxic effects of IMNB and that monitoring for cardiac troponin I may provide a sensitive means of detecting IMNB toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3584.
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